eligibility_summary
Inclusion: Active MM with measurable disease and t(11,14), ≥1 prior line incl PI, lenalidomide, steroids, progressive, ECOG ≤2, labs: ANC ≥1.5, platelets ≥75, Hb ≥8, CrCl ≥30, contraception required. Exclusion: intolerance, amyloidosis/POEMS, HIV/active HBV/HCV, significant CV disease or recent surgery/infection, recent anti‑CD38 or no ≥MR, prior venetoclax, recent anti‑cancer/experimental therapy, CYP3A inhibitors/inducers and grapefruit/Seville/starfruit, caution with warfarin/P‑gp/BCRP/OATP.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 single-arm trial in relapsed/refractory multiple myeloma with t(11,14) testing: 1) Venetoclax—oral small-molecule BCL-2 inhibitor (BH3 mimetic) that blocks anti-apoptotic BCL-2 to trigger mitochondrial apoptosis (BAX/BAK). Activity is enriched in t(11,14) MM with BCL-2 overexpression, resistance linked to high MCL-1 (low BCL-2/MCL-1 ratio). 2) Isatuximab—humanized IgG1 monoclonal antibody against CD38 on myeloma cells, mediating ADCC, CDC, ADCP, and direct pro-apoptotic effects, with immune-modulating activity. 3) Dexamethasone—glucocorticoid with lympholytic, pro-apoptotic effects that enhances anti-myeloma activity. Targets/pathways: CD38+ clonal plasma cells, intrinsic apoptosis pathway via BCL-2 family, immune effector mechanisms (NK cells, macrophages, complement).